Chemicals and Drugs Commons^™

Liposomal Delivery Of Remdesivir For Localized And Targeted Treatment Of Covid-19, Anupama Melam

McKelvey School of Engineering Graduate Student Theses & Dissertations

Liposomal delivery of Remdesivir for localized and targeted treatment of COVID-19

COVID-19 is a serious, and in many cases lethal, disease that is caused by infection of the upper respiratory tract by the novel betacoronavirus, SARS-Cov-2 virus. This disease has a very high mortality rate and has affected the world in a global pandemic. SARS-Cov-2 binds to the ACE2 receptor via the receptor-binding domain (RBD) in the S protein. After this, the virus fuses with the cell membrane by the formation of a six-helix bundle. Thus, the S protein plays a major role in ensuring that the virus attaches to …

Adverse Health Effects Of Kratom: An Analysis Of Social Media Data, Abdullah Wahbeh, Tareq Nasralah, Omar El-Gayar, Mohammad A. Al-Ramahi, Ahmed El Noshokaty

Computer Information Systems Faculty Publications (Archived)

This study investigates the adverse healthcare effects associated with the use of kratom. Using machine learning techniques, we analyzed a total of 36,516 users’ posts related to kratom. The results and analysis showed that social media could help identify important insights related to the use of kratom. The sentiment and emotion analyses showed that the kratom experience was negative and largely associated with anger, fear, disgust, and sadness. The results from. topic modeling showed that kratom is associated with a number of healthcare issues such as rashes and itching, urination, constipation, loss of appetite/weight, dry mouth, seizures, nausea, heartburn, dehydration, …

The Utility Of Hyperbaric Oxygen Therapy In Post-Transplant Cyclophosphamide-Induced Hemorrhagic Cystitis: A Case Report And Review Of The Literature., Moayed Ibrahim, Kshama Bhyravabhotla, Basil Khalaf, Keith Van Meter, Nakhle S Saba, Hana Safah, Francisco Socola

School of Medicine Faculty Publications

Background: To date, there are only a few case reports of cyclophosphamide (Cy)-induced hemorrhagic cystitis (HC) in adult or pediatric allogeneic stem cell transplant (SCT) patients treated successfully with hyperbaric oxygen (HBO). In all the reported cases, Cy was used as a part of the conditioning regimen, rather than post-transplant for graft-versus-host-disease (GVHD) prophylaxis. More recently, the risk of HC in allogeneic SCT is further increased by the widespread use of post-transplantation cyclophosphamide (PTCy) as a highly effective strategy for GVHD prophylaxis. This is the first case reported of PTCy-induced HC successfully treated with HBO to the best of our …

Acute Fish Oil Supplementation And Aspirin Treatment Modulates Lipid Profile In Platelet Rich Plasma: A Randomized Pilot Trial, Joshua M. Morriss, Lisa A. Turner, Danielle M. Mccormack, Daniel Contaifer, Naren Gajenthra Kumar, Saidheeraj Paravataneni, Monther Alsultan, Suad Alshammari, Silas Contaifer, Parthasarathy Madurantakam, Dayanjan Wijesinghe

Pharmacotherapy and Outcomes Science Publications

Aims: Platelet rich plasma (PRP) has been used in tissue repair to treat numerous inflammatory pathophysiologies. Recent studies have elucidated that the bioactive lipid fraction of PRP significantly contributes towards the resolution of inflammation. There has been great interest in how therapeutics could modulate the PRP lipidome to formulate a more pro-resolving matrix. Many of the pathways used to produce either pro-resolving or pro-inflammatory lipids are shared between ω-3 and ω-6 polyunsaturated fatty acids (PUFA). Here, we explored the separate and interacting effects acute exogenous ω-3 PUFA supplementation and aspirin had on the lipidome of PRP within 6 hours.

Methods: …

Association Of Electronic Prescription In Controlled Substances Used, Archana Suwal, Jemima Akinyi Okonjo

Theses, Dissertations and Capstones

Introduction: Controlled substances have been described as pharmaceuticals or illegal medicines that act primarily on the central nervous system and could cause physical and mental dependence, eventually leading to addiction. Prescription opioids were a significant contributor to the opioid epidemic, accounting for more than 70,000 opioid-related overdose deaths, including illicit and prescription opioids, between 2018 and 2019. The Electronic Prescriptions for Controlled Substances (EPCS) initiative recently aimed to reduce rates of prescription opioid addiction, abuse, diversion, and death. The system for controlled substances had become more widely used as providers and governments trying to combat the opioid problem. Because …

Mechanisms Of Apoptosis Induced By Actinomycin D In Aerodigestive Tract Cancers, Adeoluwa Ayodeji Adeluola

Theses, Dissertations and Capstones

Upper aerodigestive tract cancers including cancers of the oral cavity, pharynx, larynx, esophagus, and lungs are the most prevalent cancers and leading causes of cancer-related deaths. Collectively, over 300,000 new cases and 146,500 deaths are projected within the US in the year 2021. Drug-associated toxicities, as well as resistance to therapy (intrinsic and acquired), are big challenges for successfully treating these cancers. Recent studies have shown that combining low-dose actinomycin D with existing therapies is a promising strategy to reduce toxicity (cyclotherapy) and to overcome resistance. The development of these treatment strategies however requires an understanding of the molecular mechanisms …

Structural Characterization And In Vitro Antiproliferative Activity Of Non-Specific Lipid Transfer Protein 1 (Nsltp1) From Fennel (Foeniculum Vulgare) Seeds, Mekdes Megeressa

Pharmaceutical Sciences (PhD) Dissertations

Non-specific lipid transfer proteins (nsLTPs) are cationic proteins involved in intracellular lipid shuttling, in growth and reproduction, as well as in defense against pathogenic microbes. Even though the primary and spatial structures of some nsLTPs from different plants indicate their similar features, they exhibit distinct lipid-binding specificities signifying their various biological roles that dictate further structural study. The present study determined the complete amino acid sequence, in silico 3D structure modeling, and in vitro antiproliferative activity of nsLTP1 from fennel (Foeniculum vulgare) seeds.

Fennel is a member of the family Umbelliferae (Apiaceae) native to southern Europe and the …

Investing Into Domestic Manufacturing Of Critical Medication And Vaccines For The Federal Government, Sharon Low

All Reports

While the federal government has made numerous public announcements regarding their stimulus plan and promises to increase the domestic capacity to produce personal protective equipment, vaccines, and medical equipment, a critical aspect that has been neglected is the serious and ongoing shortages of critical medication. The government has promised to provide 4.28 billion to expand testing and contact tracing capacities, 7.5 billion towards PPE, and 500 million to the provinces and territories for “critical health care system needs and support for mitigation effects.” While these efforts as part of Trudeau’s Safe Restart Agreement are a good place to begin reducing …

Amphiphilic Cell-Penetrating Peptides Containing Natural And Unnatural Amino Acids As Drug Delivery Tools And Antimicrobial Agents, David Salehi

Pharmaceutical Sciences (MS) Theses

Cell-penetrating peptides containing arginine as positively charged residues and tryptophan or diphenylalanine as hydrophobic residues were synthesized. The synthesis was accomplished through the Fmoc solid-phase peptide synthesis in the presence of HBTU and DIPEA. The side-chain protected linear peptides were cleaved from the resin and cyclized in the presence of DIC and HOAt in the solution phase overnight. MALDI-TOF mass spectrometry was used to characterize the peptides.

The cytotoxicity of the synthesized peptides was determined in CCRF-CEM (human, lymphoblast peripheral blood), and HEK-293 (human, embryonic epithelial kidney healthy) cells using the MTS assay. A concentration of 10 µM was found …

The Effects Of Bioidentical Hormone Replacement Therapy On Irritability In Menopausal Women, Giavana Hanna

Honors Undergraduate Theses

The start of the menopausal transition involves the introduction of various somatic, urogenital, and psychological symptoms; of the symptoms, irritability is one of the main complaints reported by women. The use of bioidentical hormone replacement therapy has become more prevalent in society, specifically treating the somatic and urogenital symptoms of the menopausal transition. This study aims to determine the effects of bioidentical hormone replacement therapy (BHRT) on irritability in menopausal women. To test the hypotheses, an online survey was distributed to women via social media and word-of-mouth. Participants were asked to respond to various questions, which were then analyzed based …

The Effect Of Microdosing Classical Psychedelics On Cognitive Performance, Michael Harris

Honors Undergraduate Theses

Public interest and scientific inquiry are currently bringing psychedelic research back into the spotlight after a decades-long respite from clinical human trials. A majority of the research during this recent renaissance has surrounded applications of psychedelics in the fields of mental health. Less attention is being focused to other research areas where psychedelics may also prove informative, such as cognition and information processing. A common trend taking place is the act of administering very small doses of psychedelics as a potential cognitive enhancer, called microdosing. With less research being focused on these areas however, it is not well documented whether …

Relationship Between Cannabis Use And Immediate, Delayed, And Working Memory Performance Among Older Adults, Madison H. Maynard

Honors Undergraduate Theses

Cannabis is increasingly accessible in the United States for recreational and/or medical use. Additionally, the Baby Boomer birth cohort exhibits a greater prevalence of cannabis use than prior generations of older adults. Past research has most frequently addressed the potential cognitive effects of cannabis use in populations of adolescents and young adults. Some of these studies suggest that cannabis use is chronically associated with worse performance on tasks of verbal working memory and executive functioning, however, due to methodological variation and a wide variety of potential confounds including duration of abstinence and frequency of use, results are still inconclusive. Through …

The Inhibition Of Growth Of S. Cerevisiae, U. Maydis, And M. Lychinidis-Dioicae By Apiaecea Plant Extracts, Jackson M Hoffman, Jared Scott, David Schultz Phd

Undergraduate Arts and Research Showcase

The Apiaceae family of plants contains over 3,500 species, many of which are used as food crops: vegetables (carrot, parsnip, celery, etc.), herbs (cilantro, fennel, dill, etc.), and spices (cumin, anise, caraway, etc.). Many spices have been shown to exhibit antimicrobial properties against both bacteria and fungi. We set out to determine if the Apiaceae spice extracts currently used in our lab for anticancer studies exhibit any antimicrobial properties. Ethanolic extracts were made from several Apiaceae seeds: Apium graveolens (celery), Cuminum cyminum (cumin), Anethum graveolens(dill), Foeniculum vulgare (fennel), Coriandrum satvium (coriander), Pimpinella ansium (anise), Trachyspermum ammi (ajwain), Carum carvi …

Inducing Compliance With Postmarket Studies For Drugs Under Fda's Accelerated Approval Pathway, Liang Xu, Hui Zhao, Nicholas C. Petruzzi

Research Collection Lee Kong Chian School Of Business

Problem definition: In 1992, the Food and Drug Administration (FDA) instituted the accelerated approval pathway (AP) to allow promising drugs to enter the market based on limited evidence of efficacy, thereby permitting manufacturers to verify true clinical benefits through postmarket studies. However, most postmarket studies have not been completed as promised. We address this noncompliance problem. Academic/practical relevance: The prevalence of this noncompliance problem poses considerable public health risk, thus compromising the original purpose of a well-intentioned AP initiative. We provide an internally consistent and implementable solution to the problem through a comprehensive analysis of the myriad complicating factors and …

Manipulating The Perineuronal Net In The Deep Cerebellar Nucleus, Deidre E. O'Dell

Graduate Theses, Dissertations, and Problem Reports (ETD)

Perineuronal nets (PNN) are a type of specialized extracellular matrix in the central nervous system. The PNN forms during postnatal development but the ontogeny of the PNN has yet to be elucidated. Studying the PNN in the rat brain may allow us to further understand the PNN’s role in development, learning, and memory. The PNN is fully developed in the deep cerebellar nuclei (DCN) of rats by post-natal day 18. By using enzymatic digestion of the PNN with chondroitinase ABC (ChABC), we studied how digestion of the PNN affects cerebellar-dependent eyeblink conditioning (EBC) and performed electrophysiological recordings from DCN neurons. …

Targeting Calcium Homeostasis For The Treatment Of Multiple Myeloma, Osama M. Elzamzamy

Graduate Theses, Dissertations, and Problem Reports (ETD)

Multiple myeloma (MM) is a hematological malignancy characterized by the neoplastic proliferation of the plasma cells. MM is a relatively rare cancer that accounts for about 1.8% of all cancers and is the second most common hematologic malignancies, and despite the advancement from untreatable to treatable malignancy, it is yet incurable. Calcium ions (Ca²⁺) play an important role as second messengers in regulating a plethora of physiological and pathological processes, hence cytoplasmic Ca²⁺ is tightly regulated with strict spatial and temporal control to initiate, maintain, and terminate appropriate signaling pathways and phenotypes including cellular proliferation, cell cycle …

A Semiparametric Modeling Approach For Analyzing Clinical Biomarkers Restricted To Limits Of Detection, Sandipan Dutta, Susan Halabi

Mathematics & Statistics Faculty Publications

Before biomarkers can be used in clinical trials or patients' management, the laboratory assays that measure their levels have to go through development and analytical validation. One of the most critical performance metrics for validation of any assay is related to the minimum amount of values that can be detected and any value below this limit is referred to as below the limit of detection (LOD). Most of the existing approaches that model such biomarkers, restricted by LOD, are parametric in nature. These parametric models, however, heavily depend on the distributional assumptions, and can result in loss of precision under …

Transcriptional Repressor Protein Based Macrolide Biosensor Development With Improved Sensitivity, Jayani A. Christopher

Graduate Research Posters

Macrolide antibiotics are in high demand for clinical applications. Macrolides are biosynthesized via giant assembly line polyketide synthases (PKS) which are arranged in a modular fashion. Combinatorial biosynthetic methods have been used to produce diversified macrolides by reprograming these modules and modifying tailoring enzymes required for post synthetic modifications. However it is challenging due to the size and complexity of PKSs. To overcome this challenge, new enzymes for macrolide diversification could be obtained by directed evolution where a large number of enzyme variants need to be screened. Therefore it is important to develop high throughput screening methods to identify the …

Science-Based Regulation Of Pharmacological Substances In Competition Horses, Jacob Machin

Theses and Dissertations--Toxicology and Cancer Biology

Current testing methodologies within equine forensic toxicology focus on arbitrary thresholds and zero-tolerance policy. Modern analytical chemistry’s limits of detection are low enough that oftentimes femtogram-per-milliliter amounts of a substance can readily be identified in both blood and urine of a horse. For most pharmacologically relevant compounds, these concentrations have no relevance to pharmacological effect. It is therefore crucial that testing methodologies to determine appropriate thresholds and cut-offs be developed that are driven by biological activity rather than arbitrary limits of detection. This dissertation looks to address this by suggesting a system of calculated Effective Plasma Concentrations by which a …

Potential Production Of Theranostic Boron Nitride Nanotubes (64cu-Bnnts) Radiolabeled By Neutron Capture, Wellington Marcos Silva, Helio Ribeiro, Jaime Taha-Tijerina

Manufacturing & Industrial Engineering Faculty Publications

In this work, the radioisotope 64Cu was obtained from copper (II) chloride dihydrate in a nuclear research reactor by neutron capture, (63Cu(n, )64Cu), and incorporated into boron nitride nanotubes (BNNTs) using a solvothermal process. The produced 64Cu-BNNTs were analyzed by TEM, MEV, FTIR, XDR, XPS and gamma spectrometry, with which it was possible to observe the formation of64Cu nanoparticles, with sizes of up to 16 nm, distributed through nanotubes. The synthesized of 64Cu nanostructures showed a pure photoemission peak of 511 keV, which is characteristic of gamma radiation. This type of emission is desirable for Photon Emission Tomography (PET scan) …

Use Of Small Molecule Fanconi Anemia Pathway Inhibitors As Sensitizing Agents To Laromustine., Sam W. Marchant

Honors Theses

Laromustine is an experimental chemotherapeutic sulfonyl hydrazine prodrug shown in clinical trials to be effective against acute myeloid leukemia. The mechanism of action of laromustine involves interstrand crosslinking, via chloroethylation, and enzyme inhibition, caused by carbamoylation. The work described herein aims to investigate whether inhibition of the replication-dependent interstrand crosslink repair Fanconi Anemia pathway further sensitizes cells to laromustine. By measuring metabolic activity immediately after drug exposure, we find laromustine to be equally as cytotoxic towards Fanconi Anemia deficient and wild type cells. However, through clonogenic assays we show Fanconi Anemia mutations sensitize cells to laromustine’s anti-proliferative effect. Furthermore, we …

Synthesis, Characterization And Photophysical Properties Of Ytterbium Complexes Of Functionalized Porphyrins And Porpholactone, Beibei Liu

Masters Theses

The unique structure and superior properties of lanthanide porphyrins enable them to be used in a broad variety of applications, especially in medical diagnosis fields. This research focuses on modifying the porphyrin ligands in various places, resulting in broader absorption in the red region and strong emission in the near-infrared region for these ytterbium(III) porphyrin complexes. The design, synthesis and characterization for DMPH₂-BDP, DMPH₂-COOH, TPLH₂ ligands and YbDMP-BDP, YbDMP-COOH complexes are described. The photophysical properties of these ligands and complexes including their absorbance, fluorescence and quantum yields are also presented. Both the synthesized ligands and …

Reward-Related Effects Of Amphetamines Administered By Electronic Cigarette, Lucas Wohler

Theses and Dissertations

While e-cigarette vaporizers are primarily used for the delivery of nicotine, they can also be used to administer a wide range of other substances of abuse including stimulants such as d-amphetamine and methamphetamine. Methamphetamine and prescription amphetamines are widely abused throughout the United States and across the world leading us to believe there may be abuse potential with vaping methamphetamine as vaping becomes increasingly popular. In the present study, methamphetamine and amphetamine vapor were assessed using vapor capture methods. The vapor samples were then analyzed using liquid chromatography mass spectroscopy (LC-MS). Three experiments were carried out to examine the abuse …

Overcoming Mechanisms Of Acquired And Innate Doxorubicin Resistance Using Nanomedicine And Tumor-Associated Macrophage Immunotherapy, Rashed M. Almuqbil

Theses and Dissertations

ABSTRACT

Overcoming Mechanisms of Acquired and Innate Doxorubicin Resistance Using Nanomedicine and Tumor-Associated Macrophage Immunotherapy

By Rashed M. Almuqbil, Pharm.D.

Director: Sandro R.P. da Rocha, PhD

Cancer is a leading cause of death worldwide. The available treatment for solid tumors may include surgery, radiotherapy, immunotherapy, and chemotherapy or a combination of all those regimens. Chemotherapy is widely used in the treatment of both lung cancers and breast cancer, including metastases, irrespective of type and stage. The poor rates of survival can be attributed to late diagnosis, and due to the development of acquired and innate chemoresistance. Lung tumors are intrinsically …

Standardization Of E-Cigarette Research: Addressing The Analysis Of Total Nicotine And Free Base Nicotine In E-Cigarettes, Vinit Gholap

Theses and Dissertations

Electronic cigarettes (e-cigarettes) are one of the major sources of exposure to nicotine, an addictive chemical. Since 2016, the Food and Drug Administration (FDA) has started regulating these products under the Tobacco Control Act yet, specifications about the nicotine content in these products have not been established. In e-cigarettes, nicotine concentration ranges from 0 to >50mg/mL. Additionally, several e-cigarette related parameters have been identified which can affect nicotine delivery to users. Of these factors, nicotine forms (protonated and free base) have been found to play a significant role in nicotine absorption profiles yet, a limited and contradictory research is available …

Drug Loaded Mesoporous Nanocarriers For The Treatment Of Aspergilliosis, Madeline Brooks, Emily Hunt

Summer Community of Scholars Posters (RCEU and HCR Combined Programs)

No abstract provided.

A Tool For Segmentation Of Secondary Structures In 3d Cryo-Em Density Map Components Using Deep Convolutional Neural Networks, Yongcheng Mu, Salim Sazzed, Maytha Alshammari, Jiangwen Sun, Jing He

Computer Science Faculty Publications

Although cryo-electron microscopy (cryo-EM) has been successfully used to derive atomic structures for many proteins, it is still challenging to derive atomic structures when the resolution of cryo-EM density maps is in the medium resolution range, such as 5–10 Å. Detection of protein secondary structures, such as helices and β-sheets, from cryo-EM density maps provides constraints for deriving atomic structures from such maps. As more deep learning methodologies are being developed for solving various molecular problems, effective tools are needed for users to access them. We have developed an effective software bundle, DeepSSETracer, for the detection of protein secondary structure …

Mechanism For The Unfolding Of The Top7 Protein In Steered Molecular Dynamics Simulations As Revealed By Mutual Information Analysis, Ognjen Perišić, Willy Wriggers

Mechanical & Aerospace Engineering Faculty Publications

We employed mutual information (MI) analysis to detect motions affecting the mechanical resistance of the human-engineered protein Top7. The results are based on the MI analysis of pair contact correlations measured in steered molecular dynamics (SMD) trajectories and their statistical dependence on global unfolding. This study is the first application of the MI analysis to SMD forced unfolding, and we furnish specific SMD recommendations for the utility of parameters and options in the TimeScapes package. The MI analysis provided a global overview of the effect of perturbation on the stability of the protein. We also employed a more conventional trajectory …

Interaction Between Genetic Risk Scores For Reduced Pulmonary Function And Smoking, Asthma And Endotoxin, Sinjini Sikdar, Annah B. Wyss, Mi Kyeong Lee, Thanh T. Hoang, Marie Richards, Laura E. Beane Freeman, Christine Parks, Peter S. Thorne, John L. Hankinson, David M. Umbach, Alison Motsinger-Reif, Stephanie J. London

Mathematics & Statistics Faculty Publications

Rationale Genome-wide association studies (GWASs) have identified numerous loci associated with lower pulmonary function. Pulmonary function is strongly related to smoking and has also been associated with asthma and dust endotoxin. At the individual SNP level, genome-wide analyses of pulmonary function have not identified appreciable evidence for gene by environment interactions. Genetic Risk Scores (GRSs) may enhance power to identify gene–environment interactions, but studies are few.

Methods We analysed 2844 individuals of European ancestry with 1000 Genomes imputed GWAS data from a case–control study of adult asthma nested within a US agricultural cohort. Pulmonary function traits were FEV₁, …

Carnosic Acid Differentially Modulates The Nrf2- Antioxidant Response In Male And Female Mice Following Experimental Traumatic Brain Injury, Jacob A. Dunkerson

Theses and Dissertations--Neuroscience

Traumatic brain injury (TBI) is a leading cause of death and disability in the United States. Each year, an estimated 2.8 million Americans are diagnosed with a TBI due to falling, motor vehicle collisions, gun violence, and sports related concussions. Although inflicted by a single event, the post-traumatic effects of TBI often develop into a life-long disease. Survivors often experience cognitive decline, memory loss, emotional instability, changes in personality, and physical disabilities. A single TBI, and more-so repetitive TBI's, place an individual at a greater risk of developing chronic neurological disorders, such as dementia or Alzheimer’s disease, earlier in life. …